Abstract: Pancreatic cancer remains one of the deadliest cancers, which is usually diagnosed in an advanced state for which there are little or no effective therapies. In this perspective, efforts have been made to identify specific subset of cells that has the capability of producing differentiated progeny of cells. There are three major types of cancer stem cells (CSCs), but the most important type of CSCs nowadays are chemoreristant and radioresistant CSCs that are resistant from both - chemotherapy and radiotherapy. Hence, these chemoresistant and radioresistant CSCs were identified, which may provide some novel therapeutic approach to treat pancreatic cancer. Increased numbers of CD44+CD24+ESA+ cells were needed to generate tumors when injected into the pancreas. Identified CD44+CD24+ESA+ pancreatic CSCs showed the stem cell properties i.e. self-renewal, the ability to produce differentiated progeny. Several signaling pathways are upregulated in the pancreatic CSCs. Sonic Hedgehog (SHh) signaling molecule expression was very high in CD44+CD24+ESA+ cells compared to other normal pancreatic epithelial cells. Cyclopamine, a steroidal alkaloid, which has both teratogenic and antitumor activities, inhibited Hh signaling thereby inhibited pancreatic cancer growth in vitro and in vivo, suggesting that this signaling pathway has an early and critical role in the development of pancreatic cancer. Inhibition of Hh signaling by cyclopamine indicates that in the near future cyclopamine can be used as a drug to show that it can show some promise in the treatment of pancreatic cancer.